MK2206 in Treating Younger Patients With Recurrent or Refractory Solid Tumors or Leukemia
|ClinicalTrials.gov Identifier: NCT01231919|
Recruitment Status : Completed
First Posted : November 1, 2010
Last Update Posted : April 29, 2014
|Condition or disease||Intervention/treatment||Phase|
|Accelerated Phase Chronic Myelogenous Leukemia Acute Leukemias of Ambiguous Lineage Acute Myeloid Leukemia/Transient Myeloproliferative Disorder Acute Undifferentiated Leukemia Aggressive NK-cell Leukemia Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative Blastic Phase Chronic Myelogenous Leukemia Blastic Plasmacytoid Dendritic Cell Neoplasm Childhood Burkitt Lymphoma Childhood Chronic Myelogenous Leukemia Childhood Diffuse Large Cell Lymphoma Childhood Grade III Lymphomatoid Granulomatosis Childhood Immunoblastic Large Cell Lymphoma Childhood Nasal Type Extranodal NK/T-cell Lymphoma Chronic Eosinophilic Leukemia Chronic Myelomonocytic Leukemia Chronic Neutrophilic Leukemia Chronic Phase Chronic Myelogenous Leukemia Intraocular Lymphoma Juvenile Myelomonocytic Leukemia Mast Cell Leukemia Myeloid/NK-cell Acute Leukemia Noncutaneous Extranodal Lymphoma Post-transplant Lymphoproliferative Disorder Primary Central Nervous System Hodgkin Lymphoma Primary Central Nervous System Non-Hodgkin Lymphoma Progressive Hairy Cell Leukemia, Initial Treatment Prolymphocytic Leukemia Recurrent Childhood Acute Lymphoblastic Leukemia Recurrent Childhood Acute Myeloid Leukemia Recurrent Childhood Anaplastic Large Cell Lymphoma Recurrent Childhood Grade III Lymphomatoid Granulomatosis Recurrent Childhood Large Cell Lymphoma Recurrent Childhood Lymphoblastic Lymphoma Recurrent Childhood Small Noncleaved Cell Lymphoma Recurrent Grade 1 Follicular Lymphoma Recurrent Grade 2 Follicular Lymphoma Recurrent Grade 3 Follicular Lymphoma Recurrent Mantle Cell Lymphoma Recurrent Marginal Zone Lymphoma Recurrent Mycosis Fungoides/Sezary Syndrome Recurrent Small Lymphocytic Lymphoma Recurrent/Refractory Childhood Hodgkin Lymphoma Refractory Chronic Lymphocytic Leukemia Refractory Hairy Cell Leukemia Relapsing Chronic Myelogenous Leukemia Secondary Acute Myeloid Leukemia Small Intestine Lymphoma Splenic Marginal Zone Lymphoma Unspecified Childhood Solid Tumor, Protocol Specific Waldenström Macroglobulinemia||Drug: Akt inhibitor MK2206 Other: diagnostic laboratory biomarker analysis Other: pharmacological study||Phase 1|
l. To estimate the maximum-tolerated dose (MTD) and/or recommended phase 2 dose of MK-2206 (Akt inhibitor MK2206) administered orally every other day (schedule 1) or once weekly (schedule 2) to children with refractory or recurrent solid malignancies, including central nervous system (CNS) tumors or lymphomas.
II. To define and describe the toxicities of MK-2206 in children with refractory solid malignancies administered on this schedule.
III. To assess the tolerability of MK-2206 at the solid tumor MTD in patients with recurrent or refractory leukemia.
IV. To characterize the pharmacokinetics of MK-2206 in children with recurrent or refractory cancer. (exploratory)
I. To preliminarily define the antitumor activity of MK-2206 within the confines of a phase 1 study.(exploratory) II. To evaluate biological activity of MK-2206 by measuring phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling in tumor and peripheral blood mononuclear cells and measure the expression of biomarkers related to AKT activation phenotypes. (exploratory)
OUTLINE: This is a dose-escalation study (part A) followed by treatment at the maximum-tolerated dose (part B).
Patients receive Akt inhibitor MK2206 orally (PO) every other day (schedule 1) OR once weekly (schedule 2) on days 1-28. Treatment repeats every 28 days for up 12 courses (1 year) in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||45 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of MK-2206, an AKT Inhibitor, in Pediatric Patients With Recurrent or Refractory Solid Tumors or Leukemia|
|Study Start Date :||January 2011|
|Primary Completion Date :||April 2013|
Experimental: Treatment (Akt inhibitor)
Patients receive oral Akt inhibitor MK2206 every other day (schedule 1) OR once weekly (schedule 2) on days 1-28. Treatment repeats every 28 days for up 12 courses (1 year) in the absence of disease progression or unacceptable toxicity.
Drug: Akt inhibitor MK2206
Other Name: MK2206Other: diagnostic laboratory biomarker analysis
Correlative studiesOther: pharmacological study
Other Name: pharmacological studies
- MTD and/or recommended phase 2 dose of Akt inhibitor MK2206 determined according to incidence of dose-limiting toxicities (DLTs) graded using CTCAE v4.0 (Part A) [ Time Frame: 28 days ]The MTD will be the maximum dose at which fewer than one-third of patients experience DLT during course 1 of therapy.
- Pharmacokinetic (PK) parameters of Akt inhibitor MK-2206 [ Time Frame: Baseline, 0.5, 1.5, 3, 6-8, 24, 48 hours day 1 course 1; pre-dose and 6-8 hours post-dose (optional) day 15 (Schedule 1); baseline, 0.5, 1.5, 3, 6-8, 24, 48 hours day 1 course 1; pre-dose days 8 and 15; 6-8 hours post-dose day 15 (optional) (Schedule 2) ]Summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).
- Antitumor activity assessed by Response Evaluation Criteria for Solid Tumors (RECIST) 1.1 [ Time Frame: Up to 30 days ]
- Levels of activation of downstream signaling molecules [ Time Frame: Up to day 15 of course 1 ]Summarized using descriptive statistics at each timepoint. The Wilcoxon signed-rank test or Friedman's test may be used as a preliminary test of change in activity over two or more timepoints.
- Mutations or amplification of upstream signaling molecules [ Time Frame: Baseline ]Summarized using descriptive statistics at each timepoint. The Wilcoxon signed-rank test or Friedman's test may be used as a preliminary test of change in activity over two or more timepoints.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01231919
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|Principal Investigator:||Maryam Fouladi||COG Phase I Consortium|